The bactericidal activity of polymorphonuclear neutrophils (PMN) is an incompletely understood, but essential, function in the host defenses against bacterial infection. The principal investigator plans to continue studies concerning the mechanisms of PMN bactericidal activity, the derangements noted in PMN bactericidal activity in various disease states and the possible role of various biochemical manipulations in enhancing PMN function. The alteration of the cell membrane that occurs during phagocytosis may well be instrumental in the initiation of subsequent metabolic events. We are interested in testing the effects of various membrane active compounds on the metabolic and morphologic parameters of PMN function in order to learn what causes the PMN to undergo such marked morphologic and metabolic post phagocytic changes. Two basic antibacterial mechanisms have been elucidated in PMN, one requiring oxygen and resulting in the production of hydrogen peroxide and the other concerned with the antibacterial properties of cationic proteins. By inhibiting first one and then the other mechanism, we hope to find out which bacteria are killed by which mechanism and which mechanisms are impaired in certain disease states. Bacteria ingested by polymorphonuclear neutrophils are protected from the lethal action of most antibiotics. Studies will be conducted to determine if this is due to failure of the antibiotics to enter the PMN or due to alterations in bacterial metabolism. These investigations should lead to better understanding of the mechanisms of phagocytosis and intracellular killing by the PMN and thus results in better understanding of abnormalities of leukocyte function seen in certain clinical situations.